The research will attempt to delimit the relative contributions of the "decending" and "supraspinal" components of the endogenous neuronal mechanisms by which the Transmission of sensory information through the CNS is controlled. Attention will be centered on those neuronal substrates which contribute to stimulation-produced analgesia (SPA) when activated by electrical stimulation applied in midline brainstem structures implicated in this phenomena (The periaqueductal gray matter, the raphe nuclei and the locus coeruleus.) The study will involve combined behavioral and physiological studies performed in the same animal. We will employ a paradigm whereby the animal (cat) is allowed to obtain a reward (milk) in exchange for tolerating a noxious stimulus (foot shock). Simultaneously, compound action potentials indicative of the responses of higher-order sensory neurons of the dorsal horn will be recorded at or near the surface of the spinal cord. Electrical stimulation will be applied through electrodes implanted in brainstem structures implicated in SPA. The effects of the brainstem stimulation on the escape threshold from the foot shock will be compared with its effects on the averaged potentials recorded from the cord. In this way we can infer the relative contribution of descending and supraspinal mechanisms. The same brainstem stimulation parameters will also be used to test for SPA against a graded mechanical stimulus applied to the foot. Sites in the brainstem from which strong SPA can be evoked will also be tested after administration of drugs which block neurotransmitters implicated in key roles in SPA. (Serotonin, the endogenous opiate ligands, and noradrenalin). Thus we may isolate pharmacologically components of the descending and supraspinal mechanisms contributing to the SPA evoked from that particular site. To delimit further the relative contributions of descending and supraspinal mechanisms to SPA, the same animal used in the chronic experiments outlined above will be lightly anesthetized and we will examine the effects of the same brain stem stimulus prameters applied at the same electrode sites on the responses of single identified dorsal horn neurons to noxious stimuli applied to the foot.